(Applicant's Abstract) Background: Chronic lung disease (CLD) is the most prevalent cause of mortality and permanent disability among surviving premature infants. Development of clinical interventions that will prevent or treat this disorder requires a basic understanding of the pathophysiologic mechanisms of pulmonary injury and repair. Clinical and Biostatistical Core investigators will collaborate with the laboratory-based principal investigators on each clinical project, providing clinical data, specimens, initial laboratory processing, data management, and biostatistical analyses. The Core group also will guide formulation of scientific questions in a clinically relevant manner and facilitate the transfer to the clinical setting of new knowledge generated in the laboratory. Environment: Two Harvard-affiliated newborn intensive care units (NICUs) provide the source populations for SCOR clinical studies. Together, Brigham and Women?s Hospital (BWH) and Beth Israel-Deaconess Medical Center (BIDMC) have more than 75 NICU beds and total nearly 10,000 deliveries and 2,000 NICU admissions, annually. A Core research group, laboratory, and specimen bank have been established and the first 260 of 315 enrolled subjects have contributed substantial clinical data and more than 750 tracheal aspirate and 300 urine samples that have been processed and stored at -80 degrees C. To the ongoing collections of data, tracheal aspirate secretions and urine, the investigators will add collection of dried filter paper blood spots from routine blood sampling. Projects: Four initial clinical projects will parallel laboratory studies. The first hypothesis to be tested is that syndecan, an extracellular effector molecule, contributes to lung injury through antiproteinase inhibition (PI: Bernfield). To test this hypothesis, the occurrence of CLD in a population-based study of infants inborn < 28 weeks gestational age will be correlated with sequential tracheal aspirate measures of: i) syndecans 1 and 4 and ii) proteinase activity following syndecan depletion. The second clinical project tests the hypothesis that complement factors C3a and C5a are associated with pulmonary injury leading to CLD (PI: Gerard). C3a mediates effects in asthma that also are seen in CLD: airway edema, mucous secretion, and bronchoconstriction. To assess the roles of the complement anaphylotoxins, they will evaluate early and late measures of C3a and C5a in tracheal aspirate secretions with respect to other proinflammatory cytokines and clinical outcomes. The investigators will use the same study design to assess the role of heme oxygenase 1 (HO-1) in CLD, investigating the hypothesis that HO-1 activity is deficient in the preterm newborn and this deficiency predisposes to CLD (PI: Kourembanas). The final study examines the role of bombesin-like peptide (BLP), a product of pulmonary neuroendocrine cells, on the occurrence of CLD (PI: Sunday). The potential role of BLP is especially intriguing because, in the baboon model of CLD, BLP is associated with acceleration of the disease process and administration of anti-BLP antibody halts CLD progression. Using sequential urine samples obtained from the same study population, the study will evaluate the hypotheses that: i) BLP increases CLD risk and ii) modulators of BLP expression (e.g., fetal exposure to cigarette smoke, glucorticoid therapy) influence CLD risk. This SCOR offers a unique opportunity to unite established laboratory and clinical scientists in the common purpose to discover new and effective ways to prevent and ameliorate CLD.